Identification of the "Vasoconstriction Inhibiting Factor" (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the AT2 Receptor
Background—The renin-angiotensin-system and especially the angiotensin peptides play a cen-tral role in blood pressure regulation. Here, we hypothesize that a yet unknown peptide is in-volved in the action of Ang-II modulating the vasoregulatory effects as a cofactor.
Methods and Results—The peptide with vasodilatory properties was isolated from adrenal glands chromatographically. The effects of this peptide were evaluated in-vitro and in-vivo, and the receptor affinity was analysed. The plasma concentration in humans was quantified in chronic kidney disease patients, heart failure patients and healthy controls. The amino acid se-quence of the peptide from bovine adrenal glands was HSSYEDELSEVL EKPNDQAE PKEVTEEVSSKDAAE, which is a degradation product of Chromogranin-A. The sequence of the peptide isolated from human plasma was HSGFEDELSEVLENQSSQAELKEAVEEPSSKDVME. Both peptides diminished significantly the vasoconstrictive effect of Ang-II in-vitro. Therefore, we named the peptide "vasoconstriction inhibiting factor" (VIF). The vasoregulatory effects of VIF are mediated by the AT2-receptor. VIF impairs Ang-II-induced phosphorylation of the p38MAPK-pathway but not of ERK1/2. The vasodilatory effects were confirmed in-vivo. The plasma concentration was significantly in-creased in renal and hear failure patients.
Conclusions—VIF is a vasoregulatory peptide which modulates the vasoconstrictive effects of Ang-II by acting on the AT2-receptor. It is likely that the increase in VIF may serve as a counter-regulatory effect to defend against hypertension. The identification of this target may help us to understand the pathophysiology of renal and heart failure and may form a basis for the develop-ment of new strategies for the prevention and treatment of cardiovascular disease.
- Received September 6, 2014.
- Revision received February 9, 2015.
- Accepted February 26, 2015.